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Diphtheria
206,939 (1921)
Measles
Mumps
Pertussis
Polio
(paralytic)
Rubella
894,134 (1941)
152,209 (1968)
265,269 (1934)
21,269 (1952)
0
0
11,647
0
57,686 (1969)
Tetanus*
1,560 (1923)
~25
Viral Vaccines
Cannot use Jenners strategy for most viral
pathogens since they dont have a safe relative
Instead, viral particles that cannot replicate or
heat, formalin, or irradiation-treated viruses
(inactivated virus vaccine) used
Ex) influenza, rabies
Alternatively, a naturally-occurring, mildly
pathogenic strain or a recombinant strain
(genetic engineering) can be used = live
attenuated virus vaccine
Ex) measles, mumps, yellow fever
Poliovirus
Fewer than 1% of infections with polivirus cause
disease, but it is a BAD one.
Multiple strains = same effect, so there was a
need for a broad-spectrum vaccine
Salk vaccine = killed virus of 3 strains (1955), but
by 1963 Sabin introduced a live version.
Does it work? Last recorded case of polio in the
US was in 1979 (thats 3 years pre-me)
Developing countries still struggle to eradicate it,
so vaccination still happens, but do we vaccinate
against smallpox anymore?
Subunit vaccines
Hepatitis B virus (HBV) immune responses
involve protective, neutralizing antibodies
against a surface antigen
Subunit vaccine = even then there was
concern that there would be infected patients
Instead = insert gene coding HBV surface
antigen into bakers yeast then grown in mass
culture.
Since 1986, about 85% of people with
immunity to HBV comes from that vaccine
Rotavirus vaccine
Wheel-shaped (rotaterota) was described in 1973
and is a leading cause of severe childhood diarrhea
Still took more than 30 years to develop an effective
vaccine. Why?
Frequent mutation, multiple coat proteins it is a LOT
like influenza, but affects GI
Enter: Jennerian science RotaTeq vaccine has five
cattle rotaviruses that are not human pathogens and
they are genetically engineered to express human
VP4 or VP7 on their surface.
The key here: cheap and easy to deliver to poor
countries
Bacterial vaccines
First live-attenuated bacterial vaccine:
Mycobacterium tuberculosis
Since: Salmonella typhi (typhoid fever) but in a
human-driven mutated strain that cannot express the
LPS toxin chain!
Some pathogen toxins are the big problem, not so
much bacterial replication itself: diptheria and tetanus
- Each vaccination for these = a booster or a toxoid (a
lot like viral subunit vaccines)
Any vaccine against a Gram+ bacteria needs to help
complement penetrate their capsule, which is a
challenge.
Conjugate vaccines
If a vaccine only activates part of the immune
response, it doesnt offer all that much protection (i.e.
need B and T cells)
Ex) Polysaccharide vaccine for Meningitis no source of
peptide for MHC-II presentation, so antibody response
was weak and T-cell response was non-existent
Solution? Conjugate vaccines = conjugate the N.
meningitidis polysaccharide to either tetanus or
diptheria toxoid. Linking epitopes that can activate both
T cells and B cells
Similar techniques are used against pneumonia-causing
agents too
Adjuvants
Subunit and conjugate vaccines of one or a few purified
peptides DO NOT activate the innate immune response
because they are not detected by TLRs and other
receptors.
To get the attention of the innate immune response,
adjuvants are used and these trigger inflammation
Ex) DTP: diptheria toxoid, tetanus toxoid, and B. pertussis
bacteria (combination vaccine): bacteria induces
inflammation AND the toxoids become targets for both
lymphocyte types
Alum is used as an adjuvant (aluminum hydroxide), but it is
weak (used since 1924), but there other safe ones in
development (see Fig. 11.21)
Experimental studies have used mercury, lead, and arsenic
to do the same, but clearly those have major side effects.
Worldwide Influenza
AKA how we almost destroyed the world 5 year ago because we
are dumbasses.
World Health Organization subsidizes companies for providing
vaccines against potentially pandemic pathogens (say that 10x
fast)
But not everyone gets a flu shot and the flu evolves rapidly, so
sometimes by the time you get it, its already changed.
In March 2009, swine flu (a novel H1N1 strain) hit Mexico and
North America. The manufacturing of a vaccine began on June 7
as the epidemic began. The epidemic peaked in October 2009,
but the vaccine was not available and delivered to patients until
December 2009 and January 2010. OOOOOPS!
Fortunately, it wasnt as deadly as it could have been but why
did it take so long????
- $$$ and Proprietary Science!
- Now we have a mandated system in place where dozens of
companies will synthesize enough vaccine in a single day to
vaccinate all of the USA if a new one arrives.
100% effective
Oral dosage form
No adverse effects
Highly immunogenic
life-long immunity
no boosters required
Cheap
Stable at room temperature
no cold chain required
http://howdovaccinescauseautism.com/